The main goal is to provide new information about the chemistry, physiology and clinical significance of plasma lipoproteins and to utilize the existing and newly acquired knowledge for the formulation of an integrated view of lipid transport processes. The conceptual framework is based on the view that the fundamental physicochemical entities of the plasma lipoprotein system are lipoprotein particles as defined by their apolipoprotein composition. Chemical studies will be concerned with further development of procedures for the immunoprecipitation and immunoaffinity chromatography of lipoprotein particles using either polyclonal or monoclonal antibodies as ligands. Other techniques to be developed include two-dimensional electrophoresis of lipoproteins, a blotting procedure for identifying minor, uncharacterized apolipoproteins and microELISA for measuring human LCAT and plasma apolipoproteins. Among other chemically-oriented projects will be further studies on the isolation and characterization of the CETP-lipoprotein complex and apolipoprotein B. These latter studies will be centered around the production and characterization of monoclonal antibodies to polymorphic forms of human ApoB and rat ApoB-100 and ApoB-48, the separation of polymorphic forms of ApoB by a fast protein liquid chromatography procedure, the exploration of the effect of lipid peroxidation on the structure of ApoB and a search for inhibitor(s) of the proteolytic degradation of intestinal ApoB-100. Metabolic studies will be concerned with further characterization of lipoprotein particles generated by partial lipolysis of VLDL and the effect of HDL and lipoprotein-depleted plasma on the degradation of triglyceride-rich lipoproteins. Other metabolic studies, to be carried out with HepG2 cells, will be aimed at characterizing the catabolism of major density lipoprotein classes from diabetic patients and on the effect of hormones and fatty acids on the secretion of lipoprotein particles. Studies on the characterization of ApoB-containing lipoprotein subspecies isolated by monoclonal antibodies to ApoB will be continued. Major objectives for the Core Laboratories will be to establish the OPA methodology for amino acid analyses, to develop a method for phospholipid class quantitation, to introduce a liquid chromatography procedure for purifying apolipoproteins and to obtain the CDC certification for the cholesterol and triglyceride methodology.